Idiopathic pulmonary fibrosis (IPF), a progressive fibrotic interstitial lung disease (ILD) with median survival of 2.5-3 years, is largely unaffected by currently available medical therapies (Kim D S et al., 2006). The disease is characterized by alveolar epithelial cell injury and activation, fibroblast/myofibroblast foci formation, and exaggerated accumulation of extracellular matrix in the lung parenchyma. Recent studies employing high-throughput genomic technologies to analyze samples from IPF patients or genetically modified animals have highlighted the complexity of the pathways involved in the disease (Kaminski N and Rosas I O, 2006; Gibson K F and Kaminski N, 2004; Keane M P et al., 2005). While these studies have improved the understanding of the molecular mechanisms underlying lung fibrosis, they did not translate well into the clinical arena.
Identification of peripheral blood biomarkers may facilitate the diagnosis and follow-up of patients with IPF as well as the implementation of new therapeutic interventions. Currently, establishing a diagnosis of IPF may require surgical lung biopsy in patients with atypical clinical presentations or high-resolution computed tomography (HRCT) scans. Patients with IPF are often evaluated by serial pulmonary physiology measurements and repeated radiographic examinations. These studies provide a general assessment of the extent of disease, but do not provide information about disease activity on a molecular level. Higher plasma concentrations of surfactant proteins (Greene K E et al., 2002), KL-6 (Yokoyama A et al., 1998), FASL (Kuwano K et al., 2002), CCL-2 Suga M et al., 1999), α-defensins (Mukae H et al., 2002), and most recently SPP1 (Kadota J et al., 2005) have been reported in patients with IPF and other ILDs but most of these studies were modest in size and assayed only a single or a few protein markers simultaneously. Matirx metalloproteinase-8 (“MMP8”) has been implicated as playing a role in tissue remodeling in IPF, but also in sarcoidosis (Henry, M T et al., (2002), making it a non-specific marker of IPF. Similarly, matrix metalloproteinase-7 (“MMP7”) was reported to be elevated in bronchoalveolar fluid from both IPF patients as well as patients suffering from cryptogenic organizing pneumonia (“COP”; Huh, J W et al., 2008).